Part One Six patients with rheumatoid arthritis (RA) unresponsive to conventional therapies have been studied in an open pilot trial of short-term pulse methylprednisolone (MP). Following administration of 1 gram of MP intravenous on 3 consecutive days, dramatic changes in articular index were evident in the first 1-2 weeks. The effect persisted for a variable period of time - 2 weeks to more than 8 weeks. No major side effects were observed. No persistent changes in several immunological parameters were measured. The results provide a preliminary basis to design better therapeutic protocols. Part Two Oral administration of high dose pulse corticosteroid is potentially a more practical method of administering pulse therapy. Drug absorption and patient acceptance, however, of high dose orally administered steroids are not well documented. Thus, we studied plasma MP levels in 3 patients with RA after a single IV or oral administration. Preliminary results indicate that orally administered high dose MP is well absorbed (greater than 60%.) and well tolerated, but therapeutic equibalence of IV versus orally administered MP is not certain.